3-cyclohexylaminopropane-1-sulphonic acid

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
The substance decomposes at ca. 327 °C before melting occurs, and consequently a very low vapour pressure (0.17 + 10exp(-6) Pa, calculated). So, the exposure to CAPS via inhalation of vapour can be disregarded as no vapour will be formed during handling. Also, the substance is not distributed as e.g. aqueous solution, so the formation of inhalable droplets or aerosols can furthermore be excluded. The substance, however, has intrinsically a particle size which needs to be regarded. The average particle size of the test substance = 4.848 µm (D10 = 1.15 µm, D50 = 4.10 µm, D90 = 9.64 µm). This results in the following fractions according to the given limit values:~ 100% are <100 µm (inhalable fraction), ~ 90% are <10 µm (thoracic fraction), and ~ 50% are < 4µm (respirable fraction). So theoretically, the inhalative route, which does not allow an assessment of the systemic toxicity as well as via the oral route, may also be relevant for humans. However, it is considered that additional testing by the inhalative route does not reveal any further valuable information. Both test data via the dermal and oral route is available, covering both the substance as such and possibly its metabolized (oral route) form.
Furthermore, testing is scientifically not necessary and would not reveal any additional information which cannot be derived from other available acute toxicity data, so that testing can be omitted due to animal welfare:
According to ECHA’s guidance, Moderate log P values (between -1 and 4) are favourable for absorption directly across the respiratory tract epithelium by passive diffusion. The log Pow of the test item 3-(Cyclohexylamino)-propane sulfonic acid was calculated as -0.778 ± 0.020 (mean ± standard deviation). As the calculated log Pow of the test item lies below the lowest log Pow of the reference items (2-Butanone with log Pow 0.3), the log Pow of the test item is stated as < 0.3. Hence, this value may indicate a certain potential for absorption. However, with a water solubility of 184 g/L at 20°C, absorption here is hindered. Further, there are no signs of toxicity obvious via the oral or dermal route.
There is no study available (and required) for the acute inhalation toxicity of CAPS; however, there are LD50 values via other application routes available:
Oral: LD50 > 2000 mg/kg, LD0 ≥ 2000 mg/kg (OECD 420, GLP)
Dermal LD50 > 2000 mg/kg, LD0 ≥ 2000 mg/kg (OECD 402, GLP)
The obtained values are consistent and can be hence considered as reliable, and may be so used for further considerations:
According to OECD guideline 403 (Acute inhalation toxicity), the concentration of respirable particles for limit testing is 5 mg/L over 4 h. Taking into account for rats a standard respiratory volume of 0.2 l/min and average body weight of 250 g (Guidance on information and requirements and chemical safety assessment, chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, ECHA, http://echa.europa.eu/web/guest/guidance-documents/guidance-on-information-requirements-and-chemical-safety-assessment), a total respiratory volume of 48 litre over 4 h can be assumed. This would result in a total dose of 240 mg per rat, which is equivalent to 960 mg/kg bw.
Assuming in a worst-case scenario that this total dose will be absorbed to 100%, and assuming furthermore that the orally applied amount is only absorbed to 50%, this dose would correspond to an oral dose of 1920 mg/kg bw. This value is below the relevant determined LD50 and even LD0 via the oral and dermal route, i.e. 2000 mg/kg bw. Hence, it can be reasonably assumed that an additional acute toxicity test via the inhalation route would reveal an LC50inhalation >5 mg/L, most likely even a LC0inhalation ≥5 mg/L. This is supported by the reasonably assumable at least partially hindered absorption via the inhalatory route compared to the oral one.
Furthermore, during the investigation of the acute dermal toxicity, no alterations of the skin were detected, and CAPS is neither a skin nor eye irritant nor a dermal sensitizer. So it can be additionally concluded, that no local effects during inhalation toxicity testing are likely occur and need to be regarded.
In consequence, the available oral and dermal acute toxicity studies are sufficient to cover this endpoint, no acute toxicity testing via inhalation route needs to be performed and can consequently be waived due to animal welfare.